Six Novel Variants in the MKRN3 Gene Causing Central Precocious Puberty.

peer reviewed[en] CONTEXT: Idiopathic central precocious puberty (iCPP) is defined by the premature reactivation of the hypothalamic-pituitary-gonadal axis with normal magnetic resonance imaging scan of the central nervous system, causing the development of secondary sexual characteristics before age 8 years in girls and 9 years in boys. MKRN3 loss of function variants now represent the most common genetic cause of iCPP. OBJECTIVE: This work aims to document the clinical course of puberty in 8 families harboring pathogenic MKRN3 variants. METHODS: This is an observational case series study of patients with CPP due to MKRN3 variants followed in a single center. RESULTS: Genetic analysis of MKRN3 was carried out in 28 unrelated patients with iCPP and a family history of paternal inheritance or no/unavailable maternal inheritance, particularly in case of very early and rapidly evolving CPP. We identified 6 novel and 2 recently described variants in the MKRN3 gene in 9 girls, 1 boy, and their family members. These mutations were all predicted to be deleterious by in silico prediction programs. CONCLUSION: We have identified 6 novel MKRN3 mutations in children with CPP. An MKRN3 loss of function should be considered after careful history pinpointing paternally inherited CPP. A family segregation study allowed the detection of an MKRN3 variant in 2 young brothers still prepubertal, raising the question of screening and management of asymptomatic prepubertal family members

Acute diarrhea in adults consulting a general practitioner in France during winter: incidence, clinical characteristics, management and risk factors

International audienceBackgroundData describing the epidemiology and management of viral acute diarrhea (AD) in adults are scant. The objective of this study was to identify the incidence, clinical characteristics, management and risk factors of winter viral AD in adults.MethodsThe incidence of AD in adults during two consecutive winters (from December 2010 to April 2011 and from December 2011 to April 2012) was estimated from the French Sentinelles network. During these two winters, a subset of Sentinelles general practitioners (GPs) identified and included adult patients who presented with AD and who filled out a questionnaire and returned a stool specimen for virological examination. All stool specimens were tested for astrovirus, group A rotavirus, human enteric adenovirus, and norovirus of genogroup I and genogroup II. Age- and sex-matched controls were included to permit a case¿control analysis with the aim of identifying risk factors for viral AD.ResultsDuring the studied winters, the average incidence of AD in adults was estimated to be 3,158 per 100,000 French adults (95% CI [2,321 ¿ 3,997]). The most reported clinical signs were abdominal pain (91.1%), watery diarrhea (88.5%), and nausea (83.3%). GPs prescribed a treatment in 95% of the patients with AD, and 80% of the working patients with AD could not go to work. Stool examinations were positive for at least one enteric virus in 65% (95% CI [57 ¿ 73]) of patients with AD with a predominance of noroviruses (49%). Having been in contact with a person who has suffered from AD in the last 7 days, whether within or outside the household, and having a job (or being a student) were risk factors significantly associated with acquiring viral AD.ConclusionsDuring the winter, AD of viral origin is a frequent disease in adults, and noroviruses are most often the cause. No preventable risk factor was identified other than contact with a person with AD. Thus, at the present time, reinforcement of education related to hand hygiene remains the only way to reduce the burden of disease

Growth response of syndromic versus non-syndromic children born small for gestational age (SGA) to growth hormone therapy: a Belgian study

IntroductionA substantial proportion of SGA patients present with a syndrome underlying their growth restriction. Most SGA cohorts comprise both syndromic and non-syndromic patients impeding delineation of the recombinant human growth hormone (rhGH) response. We present a detailed characterization of a SGA cohort and analyze rhGH response based on adult height (AH).MethodsClinical and auxological data of SGA patients treated with rhGH, who had reached AH, were retrieved from BELGROW, a national database of all rhGH treated patients held by BESPEED (BElgian Society for PEdiatric Endocrinology and Diabetology). SGA patients were categorized in syndromic or non-syndromic patients.Results272 patients were included, 42 classified as syndromic (most frequent diagnosis (n=6): fetal alcohol syndrome and Silver-Russell syndrome). Compared with non-syndromic patients, syndromic were younger [years (median (P10/P90)] 7.43 (4.3/12.37) vs 10.21 (5.43/14.03), p=0.0005), shorter (height SDS -3.39 (-5.6/-2.62) vs -3.07 (-3.74/-2.62), p=0.0253) and thinner (BMI -1.70 (-3.67/0.04) vs -1.14 (-2.47/0.27) SDS, p=0.0054) at start of rhGH treatment. First year rhGH response was comparable (delta height SDS +0.54 (0.24/0.94) vs +0.56 (0.26/0.92), p=0.94). Growth pattern differed with syndromic patients having a higher prepubertal (SDS +1.26 vs +0.83, p=0.0048), but a lower pubertal height gain compared to the non-syndromic group (SDS -0.28 vs 0.44, p=0.0001). Mean rhGH dose was higher in syndromic SGA patients (mg/kg body weight/day 0.047 (0.039/0.064) vs 0.043 (0.035/0.056), p=0.0042). AH SDS was lower in syndromic SGA patients (-2.59 (-4.99/-1.57) vs -2.32 (-3.3/-1.2), p=0.0107). The majority in both groups remained short (<-2 SDS: syndromic 71%, non-syndromic 63%). Total height gain was comparable in both groups (delta height SDS +0.76 (-0.70/1.48) vs +0.86 (-0.12/1.86), p=0.41).ConclusionsCompared to non-syndromic SGA patients, syndromic SGA patients were shorter when starting rhGH therapy, started rhGH therapy earlier, and received a higher dose of rhGH. At AH, syndromic SGA patients were shorter than non-syndromic ones, but their height gain under rhGH therapy was comparable

Feeding mice with diets containing mercury-contaminated fish flesh from French Guiana: a model for the mercurial intoxication of the Wayana Amerindians

International audienc

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Altimetry for the future: building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Five Studies in Developmental Endocrinology: Ætiological, Clinical, and Outcome aspects

Les affections endocriniennes du développement sont des maladies rares que soigne et étudiele pédiatre-endocrinologue. Elles nous renseignent sur de nombreux aspects du développement normalet du fonctionnement du système endocrinien.Ce travail regroupe des études cliniques qui concernent différentes glandes endocrines. Toutd’abord l’hypophyse, dont trois aspects sont abordés. Une nouvelle étiologie d’hypopituitarismecongénital syndromique associant anophtalmie et fente palatine est décrite. Le gène impliqué, RAX, estconservé chez tous les vertébrés et était connu chez l’homme pour donner une anophtalmie isolée.L’étude fait le parallélisme entre les phénotypes humain et murin, qui sont remarquablement similaires.Un autre aspect de la pathologie du développement hypophysaire est illustré par une étude del’hypopituitarisme congénital non syndromique dont le diagnostic est fait tardivement en raison descirconstances de vie défavorables des patients. La neurohypophyse est abordée par l’étude de troisfamilles avec diabète insipide central autosomique dominant associé à un retard de croissance. Lapathophysiologie de celui-ci est discutée à la lumière de données de physiologie murine sur l’anorexiepar déshydratation. Ensuite, le syndrome triple A, pléiotrope car lié à un déséquilibre Redox, est étudiésous l’angle de son atteinte rétinienne qui ouvre une fenêtre sur le caractère neurodégénératif de lamaladie. Finalement, le suivi à long terme d’une cohorte de patients avec hypothyroïdie congénitaleillustre les causes et conséquences des anomalies développementales ou fonctionnelles de la thyroïde.Le fil d’Ariane entre les différentes composantes de ce travail est d’illustrer l’importance:- de l’interprétation des observations cliniques à la lumière des connaissances de la physiologie humaineet animale.- d’une description phénotypique minutieuse pour la prise en charge optimale des patients et pour larecherche clinique.Doctorat en Sciences médicales (Médecine)info:eu-repo/semantics/nonPublishe

Central precocious puberty after interpersonal transfer of testosterone gel: just a coincidence?

Over the last 10 years, several children, fetuses and women have been reported to be virilized through interpersonal transfer of testosterone (T) gel used by fathers or partners. Long-term exposure to androgens in children, such as in poorly controlled congenital adrenal hyperplasia, is known to promote central precocious puberty.Case ReportsJournal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Children's virilization and the use of a testosterone gel by their fathers

We report severe virilization in three unrelated children by contact with their fathers, who had been using a testosterone lipogel. © Springer-Verlag 2005.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Nephrogenic syndrome of inappropriate antidiuresis in a female neonate: Review of the clinical presentation in females

Background: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare X-linked disease due to gain-of-function mutations in the AVP V2 receptor gene. Hemizygous males present with recurrent episodes of severe hyponatremia in in-fancy. Heterozygous females are usually asymptomatic. Case Report: We report on a 23-day-old female neonate, born at term with 3,260 g that presented with recurrent hyponatremia (Na between 124 and 134 mmol/l) due to NSIAD. She was a heterozygous carrier of the c.409 C>T mutation in the AVPR2 gene. Conclusions: This is the first report of a female neonate presenting with hyponatremia due to NSIAD. The diagnosis of NSIAD should not be limited to male infants and should also be considered in female infants with the clinical picture of inappropriate antidiuresis.SCOPUS: re.jinfo:eu-repo/semantics/publishe